[The quality of antibiotic treatment in primary health care in the county of Osona (Barcelona)].
The evaluation and quality control of antibiotic prescription has become widespread in primary health care (PHC). Most of the studies performed have analyzed the quality of the drug and not the treatment. The aim of this study was to evaluate the quality of the antibiotic treatments of physicians in a concrete area and identify the most deficient aspects. A prospective study was performed with the voluntary participation of general physicians and pediatricians of the PHC area of Osona (Barcelona, Spain) by the collection of a series of data of each antibiotic treatment carried out over 30 days. Consideration of each item to evaluate the quality of a given treatment was carried out by a nominal group. A total of 1,976 antibiotic treatments were administered by the 44 physicians participating in the study (68% of the target population). The aspect found to be most deficient was that 20% of the doctors prescribed an antibiotic in a diagnosis for which it was not susceptible and in 30% of the susceptible cases the choice of antibiotic was erroneous. The length of treatment was the aspect on posology showing the worst results (27% incorrect). The mean quality following the application of the scale elaborated by the nominal group was 72.6 (SD = 25.7) over a maximum of 100. Lower quality was observed in the pediatricians (p = 0.006), in the physicians working in the reformed network (p < 0.0001), in the prescriptions induced by another physician (p = 0.0001) and in those induced by the patient (p = 0.03). The number of antibiotics prescribed in non susceptible processes in primary health care should be reduced. Likewise, the choice of antibiotics prescribed should improve.


Correlation of hepatitis B surface antigen expression with clinicopathological and biochemical parameters in liver biopsies: A comprehensive study.
Chronic viral B hepatitis (CHB) is a potentially life-threatening liver disease that may progress to liver failure and cirrhosis. Currently, although combinations of different laboratory methods are used in the follow-up and treatment of CHB, the failure of these procedures in some cases has led to the necessity of developing new approaches. In CHB, the intrahepatic expression pattern of viral antigens, including hepatitis B surface antigen (HBsAg), is related to different phases of inflammation. However, many studies have focused on the intracytoplasmic properties of HBsAg staining, and HBsAg positivity in liver tissue has not been evaluated by objective quantitative methods. To investigate the relationship of image analysis-based quantitative HBsAg expression and its staining patterns with clinicopathological factors and treatment in CHB. A total of 140 liver biopsies from treatment-naïve cases with CHB infection were included in this study. Following diagnosis, all patients were treated with entecavir (0.5 mg) and followed up at three-month intervals. The percentage of immunohistochemical HBsAg (p-HBsAg) expression in the liver was determined in whole tissue sections of biopsies from each case by image analysis. The immunohistochemical staining pattern was also evaluated separately according to 3 different previously defined classifications. A positive correlation between p-HBsAg and serum levels of hepatitis B virus (HBV) DNA and HBsAg was observed (P < 0.001). The p-HBsAg value was significantly higher in younger patients than in older patients. When the groups were categorized according to the hepatitis B e antigen (HBeAg) status in HBeAg-positive cases, p-HBsAg was correlated with HBV DNA, hepatitis activity index (HAI) and fibrosis scores (P < 0.001). In this group, p-HBsAg and HBsAg expression patterns were also correlated with the viral response (VR) and the serological response (SR) (P < 0.001). Multivariate analysis revealed that p-HBsAg was an independent predictor of either VR or SR (P < 0.001). In HBeAg-negative patients, although HBsAg expression patterns were correlated with both HAI and fibrosis, no relationship was observed among p-HBsAg, clinicopathological factors and VR. In pretreatment liver biopsies, the immunohistochemical determination of HBsAg expression by quantitative methods, beyond its distribution within the cell, may be a good predictor of the treatment response, especially in HBeAg-positive cases.


Decreased carotid arterial resistance in cats in response to trigeminal stimulation.
Stimulation of the trigeminal nerve or ganglion in the cat caused a frequency-dependent reduction in carotid vascular resistance. Systemic arterial blood pressure (SABP) decreased at low frequencies (0.2 to 5 sec-1) and increased at higher frequencies, thus increasing carotid blood flow at the higher frequencies. The effect on resistance was predominantly ipsilateral and was unaltered by cervical sympathectomy, but was abolished or substantially reduced by section of the trigeminal root proximal to the ganglion. Diminution of carotid vascular resistance was replicated by stimulation of the greater superficial petrosal (GSP) nerve without any change in SABP. Section of the seventh cranial nerve reduced or abolished the response to stimulation of the trigeminal nerve but not that from the GSP nerve. The trigeminal response was prevented by ganglion-blocking drugs in seven out of eight cats. The resistance response was unaffected by noradrenergic, cholinergic, serotonergic, and histamine-2 blocking agents. No neural connection could be demonstrated between the GSP and the trigeminal ganglion, and the vascular response to GSP stimulation persisted after trigeminal section. It is concluded that activation of the trigeminal system increases carotid blood flow by a pathway involving the seventh cranial nerve, the GSP and Vidian nerves, and a parasympathetic synapse employing an unconventional transmitter. A varying proportion of the response (greatest in the third division) may be mediated by antidromic activation of trigeminal nerves. These findings may have clinical implications for the vascular changes of migraine and other facial pain.


Bone strain in the equine tibia: an in vivo strain gauge analysis.
Rosette strain gauges were bonded to the cranial, caudal, and medial surfaces of the tibia in the middiaphyseal region of 6 adult ponies. While the ponies were walking, the cranial side was mainly subjected to tension, and the caudal side, to compression. The compression strain on the caudal side was 1.5 times greater than the tension strain on the cranial side. None of these principal strains was aligned along the long axis of the bone; both deviated laterally from the long axis. On the medial surface, the principal strain deviated caudally about 40 degrees from the long axis. From analysis of the strain patterns on the 3 sides of the bone, it could be concluded that during loading of the tibia, torsion was superimposed on craniocaudal bending. The strain pattern was not affected after transection of the cranial tibial muscle, as determined by measuring with the same gauges before and after surgical interference. The contribution of the cranial tibial muscle in reducing the strain in the tibial cortex was therefore very small.


How to adapt the implantation technique for the new SAPIEN 3 transcatheter heart valve design.
The new balloon-expandable Edwards SAPIEN 3 THV has significant design improvements requiring adjustments in the implantation technique as compared to the previous generation SAPIEN XT. Basically, the new valve requires less oversizing due to the outer skirt, which, if positioned underneath the annulus, can reduce the occurrence and severity of paravalvular leak (PVL). As with any transcatheter vale, a thorough assessment of the device-landing-zone, the surrounding structures, and the distribution of calcifications is of vast importance. Once the SAPIEN 3 valve is positioned with the initial orientation of the middle balloon marker at the level of the leaflet hinge points, the outer skirt will remain under the annulus, despite the foreshortening of the lower inflow portion of the valve. If there is an incomplete apposition, the outer skirt can conform to the anatomy, close the gaps, and reduce the risk of PVL. When calcifications are located on the edges of the annulus, PVL is common with the SAPIEN XT THV but dramatically reduced with the SAPIEN 3 THV. If the calcification extends from the annulus into the entire LVOT, there is always an incomplete apposition of the either valve frame; however, the resulting PVL is reduced by the outer skirt of the SAPIEN 3. In 165 consecutive SAPIEN 3 patients, 89.7% (n = 145) had none or a trace PVL and there were no patients with moderate or severe PVL. The new generation SAPIEN 3 valve allows more challenging anatomies to be treated, requires less oversizing, and can reduce PVL.


The Hemobag: the modern ultrafiltration system for patients undergoing cardiopulmonary by pass.
The return of extracorporeal circuit blood at the termination of cardiopulmonary bypass (CPB) is an important feature of blood conservation during cardiac surgery procedures globally. We report our initial clinical evaluation of the Hemobag system a blood-salvaging device designed for whole blood recovery of residual post-CPB volume. Residual whole blood is hemoconcetrated through the multipass "recovery loop" circuit separate from the CPB and collected in the Hemobag System. This allows the surgeons to continue with surgery, decannulate, and administer protamine simultaneously while the Hemobag is in use and the CPB circuit remains safely primed. We have compared 25 patients receiving the Hemobag to a control group of 25 patients treated with the cell washer that represented our previous standard of care method of circuit blood-salvaging technique. The Hemobag system provided significantly higher hemoglobin, hematocrit, fibrinogen, albumin, and total protein levels in the final product reducing the amount of wasted autologous blood cells. There were no device-related complications. There were no significant differences in terms of blood utilization, chest tube drainage and clinical outcomes over the entire postoperative period among groups. These results suggest that the Hemobag system is a safe and efficient method to multipass hemoconcentrate the residual diluted blood of the CPB circuit. The Hemobag has demonstrated its ability to maximize the composition of the residual CPB volume to achieve the best possible post-CPB hemoglobin, plasma protein and coagulation factors profile for the patient respect to CW.


Chronotropic incompetence in patients with an implantable cardioverter defibrillator: prevalence and predicting factors.
Chronotropic incompetence (CI), which has not been systematically examined in the ICD patient population, may have implications for device programming. A total of 123 ICD patients were classified into three groups: single-chamber ICD with sinus rhythm, dual-chamber ICD with sinus rhythm, and single-chamber ICD with permanent atrial fibrillation. Heart rate response, maximum oxygen uptake, and oxygen uptake at the anaerobic threshold were measured during treadmill exercise testing. In addition, clinical variables such as antiarrhythmic drug therapy, underlying heart disease, and left-ventricular (LV) ejection fraction were recorded. Of the patients studied, 38% were chronotropically incompetent (47/123). Significant predictors of CI were as follows: presence of a coronary disease (P = 0.036), prior cardiac surgery (P = 0.037), chronic drug therapy with beta-blockers (P = 0.032), administration of amiodarone (P = 0.025), and a combination of these two forms of treatment (P = 0.01). Spiroergometry revealed reduced exercise capacity (P = 0.041) and lessened VO2max (P = 0.034) among chronotropically incompetent patients. A large percentage of ICD patients demonstrates CI with subsequently reduced physical stress tolerance. In light of the DAVID study, we believe that a closer examination of rate-adaptive modes for ICD patients is warranted under enhanced conditions: (1) optimized AV interval programming; (2) utilization of new algorithms to reduce ventricular pacing in combination with rate-adaptive atrial pacing, with the goal of addressing CI while minimizing ventricular pacing; and (3) an optimized upper heart-rate limit.


Designer Metallic Acceptor-Containing Halogen Bonds: General Strategies.
Being electrostatic interactions in nature, hydrogen bonding (HB) and halogen bonding (XB) are considered to be two parallel worlds. In principle, all the applications that HB have could also be applied to XB. However, there has been no report on an anionic, metallic XB acceptor, but metal anions have been observed to be good HB acceptors. This missing mosaic piece of XB theory is because common metal anions are reactive for XB donors. In view of this, two strategies are proposed for designing metallic acceptor-containing XB using ab initio calculations. The first one is to utilize a metal cluster anion with a high electron detachment energy, such as the superatom, Al13- as the XB acceptor. The second strategy is to design a ligand-passivated/protected metal core that can maintain the negative charge; several exotic clusters, such as PtH5- , PtZnH5- , and PtMgH5- , are used as examples. Based on these two strategies, it is anticipated that more metallic acceptor-containing XBs will be discovered.


Shallow size-density relations within mammal clades suggest greater intra-guild ecological impact of large-bodied species.
Population densities of species have a predictable relationship with their body mass on a global scale. This relationship is known as the size-density relationship (SDR). The relationship was originally found to be directly opposite of metabolic rate scaling, which led to the hypothesis of energetic equivalence. However, recent studies have suggested that the SDR varies between clades. Specifically, the SDR for certain mammal clades has been found to be less negative than the relationship across all mammals. The aim of the present study is to estimate phylogenetic variation in the scaling relationship, using a data-driven identification of natural phylogenetic substructure in the body size-density relation, and discuss its potential drivers. The classic model is often used to estimate natural population densities, and a further, practical aim is to improve it by incorporating variability among phylogenetic groups. We expand the model for the SDR relation of mammals to include clade-specific variation. We used a dataset with population and body mass estimates of 924 terrestrial mammal species, covering 97 families, and applied an algorithm identifying group-specific changes in the relationship across a family-level phylogeny. We show increased performance in species density estimation is achieved by incorporating clade-specific changes in the relationship compared to the classic model (increasing r2 from .56 to .74 and ΔAICc = 466). While the global SDR across clades was confirmed to be similar to previous findings (r = -.74), the relationship within all sub-clades was less negative than the overall trend. Our results show that data-driven identification of phylogenetic substructure in the size-density relation substantially improves predictive accuracy of the model. The less negative relationship within clades compared to the overall trend and compared to within clade metabolic scaling suggest that the energetic equivalence rule does not hold. This relationship shows that large species within clades use proportionally more energy than smaller species. Therefore, our results are consistent with a greater intra-guild ecological impact of large-bodied species via partial monopolisation of resources by the largest species of a given guild, and hence size-asymmetric intra-guild competition.


Identifying the types of missingness in quality of life data from clinical trials.
This paper discusses methods of identifying the types of missingness in quality of life (QOL) data in cancer clinical trials. The first approach involves collecting information on why the QOL questionnaires were not completed. Based on the reasons provided one may be able to distinguish the mechanisms causing missing data. The second approach is to model the missing data mechanism and perform hypothesis testing to determine the missing data processes. Two methods of testing if missing data are missing completely at random (MCAR) are presented and applied to incomplete longitudinal QOL data obtained from international multi-centre cancer clinical trials. The first method (Ridout, 1991) is based on a logistic regression and the second method (Park and Davis, 1993) is based on an adaptation of weighted least squares. In one application (advanced breast cancer) missing data was not likely to be MCAR. In the second application (adjuvant breast cancer) the missing mechanism was dependent on the QOL scale under study. MCAR and missing at random (MAR) have distinct consequences for data analysis. Therefore it is relevant to distinguish between them. However, if either MCAR or MAR hold, likelihood or Bayesian inferences can be based solely on the observed data, although for MAR, depending on the research question, modelling the dropout mechanism may still be necessary. Distinguishing between MAR and missing not at random (MNAR) is not trivial and relies on fundamentally untestable assumptions.


Comparison of the serum and salivary antibodies to detect gastric Helicobacter pylori infection in Kashan (Iran).
Helicobacter pylori (H. pylori) is an important and common contagious human pathogen which may cause peptic ulcer and also gastric cancer. The definite diagnosis of it is made through invasive tests. Recently, non-invasive tests including serologic tests of serum and saliva have been conducted for diagnosis of H. pylori infection. In this research, the diagnostic values of serum and salivary serology were compared together to use salivary anti-H. pylori test as an alternative method in the future. During this prospective case-control study on patients who were candidates for endoscopy and gastric biopsy from March 2015 to April 2016 in Shahid Beheshti hospital, Kashan, Iran, serum and salivary samples were obtained for measurement of Immunoglobulin G (IgG) antibody levels against H. pylori by enzyme-linked immunosorbent assay (ELISA). Histopathology was the gold standard test. Statistical analysis was performed by SPSS software version 16. Statistical tests included Kolmogorov-Smirnov, independent-samples t-test, Chi-square, Mann-Whitney U, Kruskal-Wallis, McNemar and correlation. Of 123 patients, sixty-one patients (49.6%) were H. pylori-positive according to histology. The median levels of anti-H. pylori antibodies in serum (p<0.001) and saliva (p<0.001) of H. pylori-positive cases were significantly higher than H. pylori-negative cases. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and accuracy of serologic tests in serum were 75%, 79%, 3.5, 0.3, 77% and for saliva were 85%, 82%, 4.7, 0.18, 84% respectively. Diagnostic values of salivary ELISA are comparable to serum ELISA and can be used as an alternative modality for diagnosis of H. pylori infection.


Lymphocytes and ischemia-reperfusion injury.
Ischemia reperfusion injury (IRI) is a common and important clinical problem in many different organ systems, including kidney, brain, heart, liver, lung, and intestine. IRI occurs during all deceased donor organ transplants. IRI is a highly complex cascade of events that includes interactions between vascular endothelium, interstitial compartments, circulating cells, and numerous biochemical entities. It is well established that the innate immune system, such as complement, neutrophils, cytokines, chemokines, and macrophages participate in IRI. Recent data demonstrates an important role for lymphocytes, particularly T cells but also B cells in IRI. Lymphocytes not only participate in augmenting injury responses after IRI, but could also be playing a protective role depending on the cell type and stage of injury. Furthermore, lymphocytes appear to be participating in the healing response from IRI. These new data open the possibility for lymphocyte targeted therapeutics to improve the short and long term outcomes from IRI.


The roles of bile salts in the uptake of beta-carotene and retinol by rat everted gut sacs.
The effects of bile salts, Tween 20 and hexadecyltrimethylammonium-bromide on the uptake of beta-[3H]carotene and [3H]retinol by rat-everted gut sacs were studied in vitro under conditions simulating those present in the intestinal lumen during lipid absorption. 2. Micellar solutions significantly enhanced uptake over emulsions. Maximum uptake occurred at the critical micellar concentration of the bile salts mixture. At higher detergent concentrations beta-carotene uptake declined sharply; retinol absorption remained high. 3. In beta-carotene absorption bile salts functioned not only as micellar solubilizers but also may have been required for interaction with the cell membrane or as a transport carrier. In retinol uptake their primary function appeared only to be micellar solubilization. Both uptake and efflux of substrates were enhanced in bile salt micellar solutions compared to the other detergents. 4. Beta-carotene cleavage and conversion to retinyl esters occurred only in bile salts solutions. Retinol esterification was seen with all detergents. These effects increased as the tri/dihydroxy bile salts ratio was increased. 5. Beta-carotene uptake appeared to be reversible and passive at low concentrations. Retinol uptake was reversible, 7-30 times more rapid, and partially inhibited by 2,4-dinitrophenol at higher concentrations. An energy-requiring step may have been rate limiting.


Call recognition in chicks of the Australian brush-turkey (Alectura lathami).
Most birds rely on imprinting and experience with conspecifics to learn species-specific recognition cues. Australian brush-turkeys (Alectura lathami) do not imprint and form no bonds with parents. They hatch asynchronously, disperse widely and meet juvenile conspecifics at an unpredictable age. Nevertheless, in captivity, hatchlings respond to other chicks. A recent study, which involved the use of robotic models, found that chicks prefer to approach robots that emit specific visual cues. Here, we evaluated their response to acoustic cues, which usually play an important role in avian social cognition. However, in simultaneous choice tests, neither 2-day-old nor 9-day-old chicks preferred the choice arm with playback of either chick or adult conspecific calls over the arm containing a silent loudspeaker. Chicks of both age classes, however, scanned their surroundings more during chick playback, and the response was thus consistent in younger and older chicks. We also presented the chicks with robotic models, either with or without playback of chick calls. They did not approach the calling robot more than they did the silent robot, indicating that the combination of visual and acoustic cues does not evoke a stronger response. These results will allow further comparison with species that face similar cognitive demands in the wild, such as brood parasites. Such a comparative approach, which is the focus of cognitive ecology, will enable us to further analyse the evolution and adaptive value of species recognition abilities.


Efficacy and safety of ozonated autohemotherapy in patients with hyperuricemia and gout: A phase I pilot study.
Gout is a common form of arthritis; however, there are currently no effective therapies available. Ozonated autohemotherapy (O3-AHT) is a controversial, but successful method of treatment for a number of diseases. The present study is the first pilot study investigating the application of O3-AHT in patients with hyperuricemia and gout. In total, 10 patients diagnosed with gout were recruited and subjected to O3-AHT. Self-reported pain visual analog scale (VAS) scores and creatinine clearance values were evaluated prior to (T0), during (after the fifth session of O3-AHT treatment; 1-4 weeks; T1) and following the treatment course (5-28 weeks; T2). At T1, the creatinine clearance rate of the patients significantly increased from 105.14±35.33 (T0) to 121.45±44.52 ml/min (t=2.165, P=0.062), while the pain VAS score decreased from 5.35±2.78 (T0) to 3.30±2.21 (t=2.004, P=0.076). However, at T2, the creatinine clearance rate decreased slightly to 111.15±36.52 ml/min, and no statistically significant difference was observed from the value at T0 (t=1.723, P=0.123). The pain VAS score further decreased to 2.30±2.66 (t=2.628, P=0.027). In conclusion, O3-AHT decreased the creatinine clearance rate and the pain VAS scores of patients with hyperuricemia and gout; thus, may be a potential effective therapeutic approach.


Current perspectives on quantitative gait analysis for patients with hemiparesis.
Hase K. Current perspectives on quantitative gait analysis for patients with hemiparesis. Jpn J Compr Rehabil Sci 2022; 13: 1-3.


Screening for drugs of abuse in urine samples from a drug addiction center.
The present analytical methods used in a laboratory monitoring urine specimens collected from patients attending one of the Drug Dependency Units are described and compared with other published methods. In particular a new and simple thin-layer chromatographic system and its application to the identification of the drugs of abuse extracted from urine samples is described. The results obtained during 1974 and February 1975 are tabulated, showing the trends in drug abuse that have occurred in one area of London during that period. The usefulness of these results and of urine monitoring in relation to the treatment of the addicts is also briefly considered.


The bacteriology of pulmonary tuberculosis in a population with high human immunodeficiency virus seroprevalence.
A public sector urban university hospital in Soweto, South Africa. To describe the utility of sputum smear microscopy and the prevalence of Mycobacterium tuberculosis resistance to antituberculosis drugs according to human immunodeficiency virus (HIV) serostatus in adults. A retrospective descriptive study of consecutive cases using a record review. We studied 412 adults with culture-proven pulmonary tuberculosis, of whom 185 (44.9%) were HIV-seropositive and had a significantly lower sputum smear positivity than HIV seronegatives (68% versus 79%, P < 0.05). Smear positivity was significantly higher in HIV-infected patients with CD4 counts < or = 50/mm3 compared to those with CD4 counts of 201-300/mm3 (P < 0.05). In patients with and those without a history of previous treatment for tuberculosis, resistance to one or more antituberculosis drugs was found in 32.2% and 13.6% of cases, respectively, while resistance to both isoniazid and rifampicin (multidrug-resistant tuberculosis [MDR]) was found in 15.3% and 4.5% of patients, respectively. There was no significant difference in resistance between HIV-positive and seronegative patients. A strong tuberculosis control programme and good surveillance will be required to prevent the further spread of MDR tuberculosis. Surveys such as these are useful for monitoring control programmes.


Reconstruction using a pedicled upper arm fillet flap after excision of a malignant peripheral nerve sheath tumor: A case report.
Non-salvageable extremities have been utilized for harvesting fillet flaps as part of the "spare parts" concept in traumatic and oncologic settings. Here we report on the use of a pedicled fillet flap of the upper arm for chest wall reconstruction after excision of a malignant peripheral nerve sheath tumor in a patient with neurofibromatosis. Pedicled flaps as part of the "spare parts" concept provide the advantage of reduced donor-site morbidity, immediate closure, intact vasculature, and adequate soft tissue coverage of large defects. Malignant peripheral nerve sheath tumor is a rare aggressive tumor with a poor prognosis that may result in large defects post resection. Limited data describes the use of pedicled fillet flaps of the upper extremity. We report the use of a pedicled fillet flap of the upper arm as a viable option that can be successfully used for coverage of soft tissue defects of the shoulder and chest wall post complex resections in an oncologic setting.


Boosting efferocytosis in alveolar space using BCG vaccine to protect host against influenza pneumonia.
Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung homeostasis. Increased efferocytosis by APs results in protection against lethal acute lung injury due to pulmonary infections whereas defective efferocytosis by APs results in chronic lung inflammation. In this report, we show that pulmonary delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis by APs. Increased efferocytosis by APs maintains lung homeostasis and protects mice against lethal influenza pneumonia. Intranasally treated wild type C57Bl/6 (WT) mice with BCG showed significant increase in APs efferocytosis in vivo compared to their PBS-treated counterparts. All BCG-treated WT mice survived lethal influenza A virus (IAV) infection whereas all PBS-treated mice succumbed. BCG-induced resistance was abrogated by depleting AP prior to IAV infection. BCG treatment increased uptake, and digestion/removal of apoptotic cells by APs. BCG significantly increased the expression of TIM4 on APs and increased expression of Rab5 and Rab7. We demonstrated that increased efferocytosis by APs through pulmonary delivery of BCG initiated rapid clearance of apoptotic cells from the alveolar space, maintained lung homeostasis, reduced inflammation and protected host against lethal IAV pneumonia.


Reversion of FMR1 Methylation and Silencing by Editing the Triplet Repeats in Fragile X iPSC-Derived Neurons.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from a CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Here, we report a strategy for CGG repeat correction using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced pluripotent stem cells derived from FXS patients. Following gene correction in FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in neural precursor cells and mature neurons. Strikingly, after removal of the CGG repeats, the upstream CpG island of the FMR1 promoter showed extensive demethylation, an open chromatin state, and transcription initiation. These results suggest a silencing maintenance mechanism for the FMR1 promoter that is dependent on the existence of the CGG repeat expansion. Our strategy for deletion of trinucleotide repeats provides further insights into the molecular mechanisms of FXS and future therapies of trinucleotide repeat disorders.


[Managerial considerations in research].
Basics for proper research are good ideas, know how and adequate resources. Essential to accomplish a research project in an efficient way is thorough planning. A research project can be divided in four organizational units. Writing of the protocol, which includes details about all relevant aspects, e.g. the research question, study design, time table and budget, second, details on data collection, third, data analysis and fourth, writing a report or manuscript for publication. A thoroughly developed protocol facilitates the communication between all involved persons and permits an efficient management of a research project.


Inpatient Antineoplastic Medication Administration And Associated Drug Costs: Institution of a Hospital Policy Limiting Inpatient Administration.
Cancer treatment costs are increasing; the global cost of antineoplastic medications rose to $83.7 billion in 2015. As a result, it is imperative for institutions to implement cost-saving strategies and to maximize reimbursement for costly medications such as antineoplastic drugs. Evaluate the necessity and drug costs of administering antineoplastic medications in the inpatient setting and explore savings associated with the 2013 implementation of an institutional policy that defined criteria necessitating inpatient administration of antineoplastic medication. We conducted a retrospective chart review of patients receiving inpatient antineoplastic medications during January, April, July, and October of 2010, 2012, 2014, and 2015 at a community teaching hospital. Necessity of chemotherapy administration during the hospital admission was determined based on adherence to institutional policy. Records of 648 patients admitted for chemotherapy were reviewed. The annualized numbers of chemotherapy regimens received during inpatient admission in 2010, 2012, 2014, and 2015 were 537, 618, 369, and 420, respectively. Of all regimens administered in the inpatient setting, 80% in 2010, 78% in 2012, 83% in 2014, and 91% in 2015 met institutional policy criteria for inpatient administration (P = 0.005). The annualized average wholesale price of antineoplastic medications administered to patients that did not meet criteria for inpatient drug administration decreased from $269,049 in 2010 to $105,447 in 2015. A trend in the chemotherapy regimens administered was apparent; only one regimen (carboplatin/paclitaxel), which is relatively inexpensive, was administered to more than 5% of patients in 2015, and all patients receiving monoclonal antibodies in 2015 met criteria for inpatient administration. Implementation of a policy defining the appropriate criteria necessitating inpatient administration of antineoplastic medications has the potential to decrease the number of inpatient administrations and associated drug costs.


A new pre-column derivatization for valienamine and beta-valienamine using o-phthalaldehyde to determine the epimeric purity by HPLC and application of this method to monitor enzymatic catalyzed synthesis of beta-valienamine.
Valienamine and β-valienamine are representative C7 N aminocyclitols with significant glycosidase inhibition activity that have been developed as important precursors of drugs for diabetes and lysosomal storage diseases, respectively. The quantitative analysis of these chiral compounds is crucial for asymmetric in vitro biosynthetic processes for converting valienone into valienamine epimers using aminotransferase. Here, we developed an efficient and sensitive method for separation and quantitative analysis of chiral valienamine using reversed-phase high-performance liquid chromatography (HPLC) through o-phthalaldehyde (OPA) pre-column derivatization of the analytes. The epimers were derivatized by OPA in borate buffer (pH 9.0) at room temperature for 30 s, separated on an Eclipse XDB-C18 (5 μm, 4.6 × 150 mm) column, eluted with 22% acetonitrile at 30 °C for 18 min, and detected by a fluorescence detector using 445 nm emission and 340 nm excitation wavelengths. The average resolution of the epimers is 3.86, and the concentration linearity is in the range of 0.02-20 μg/ml. The method proved to be effective, sensitive, and reliable with good intra- and inter-day precision and accuracy, and successfully evaluated the enantiopreference and catalytic capability of the potential aminotransferases on an unnatural prochiral substrate, facilitating the design of an asymmetric biosynthetic route for optically pure valienamine and β-valienamine.


Simultaneous measurement of velocity, diameter, flow and pressure in the ascending aorta of cats. Evaluation of an extractable Doppler ultrasound probe for continuous monitoring of aortic blood flow.
To evaluate an extractable Doppler ultrasound probe designed for monitoring postoperative aortic flow in infants, simultaneous measurements of velocity, diameter, electromagnetic flow estimates, and pressure in the ascending aorta were recorded in cats. Doppler flow calculators were designed to provide flow estimates based on preset constant or measured instantaneous aortic diameter. Doppler sample volume was extended to about 1.2 X 1.6 X 4.0 mm. By pharmacological interventions, a wide range of flow rates and pressures were obtained, some of which were outside physiological values. The prototype probe described here was well suited for implantation in aortas with outer diameter 8-12 mm. Correlation coefficients between Doppler and electromagnetic estimated flow for 140 samples were 0.908 and 0.959 for constant and instantaneous diameter, respectively. Mean difference between the two methods was calculated, as well as the 95% confidence limits (2SD) of the differences. Limits of agreement, in stable haemodynamic situations without drugs, were -20.0 and 22.4% of mean average flow for constant diameter Doppler flow estimates, and -14.5 and 15.1% of electromagnetic flow values for instantaneous diameter estimates. These limits increased when all samples were taken into account, but the limits for instantaneous diameter estimates were reduced from -33.1 and 32.4 to -23.9 and 19.3% after removal of data obtained during isoprenaline infusion, which introduced extreme high flow/low pressure situations. This Doppler method seems well suited for postoperative monitoring of aortic flow in infants. Errors observed in larger aortas with an asymmetric flow profile do not seem to be present in smaller vessels within normal values of flow and pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasmablastic transformation of chronic lymphocytic leukemia: a review of literature and report on 2 cases.
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in adults in Western countries. Transformation of CLL/SLL to plasmablastic lymphoma (PBL) is exceedingly rare and often has an extremely poor response to treatment. A thorough molecular workup may help in determining clonality-relatedness and prognosis. We describe two cases of CLL/SLL that transformed into PBL, with an extensive molecular workup in one case, and a review of the literature.


Autoimmune pulmonary alveolar proteinosis successfully treated with lung lavage in an adolescent patient: a case report.
Pulmonary alveolar proteinosis is a rare interstitial lung disease characterized by accumulating surfactant materials in the alveoli. The autoimmune form is by far the most common in adults, while in the pediatric age group, the vast majority of cases are congenital. We report a case of an adolescent patient diagnosed with autoimmune pulmonary alveolar proteinosis, which is unusual in this age group. A-15 year-old Saudi male presented to the emergency department with a history of shortness of breath and low oxygen saturation. High-resolution computed tomography of his chest showed a global crazy-paving pattern. Autoantibodies against granulocyte-macrophage colony-stimulating factor were detected in his serum. A diagnosis of the autoimmune form of pulmonary alveolar proteinosis was confirmed after excluding other possible causes. The patient improved after he underwent whole lung lavage under general anesthesia, and he was independent of oxygen therapy after 6 months of follow-up. The autoimmune form of pulmonary alveolar proteinosis is rare in the pediatric age group and should be considered when no apparent cause of this disease was found. Whole lung lavage should be the first treatment modality offered in this setting with close follow-up and monitoring.


Homeostatic regulation of ribosomal proteins by ubiquitin-independent cotranslational degradation.
Ribosomes are the workplace for protein biosynthesis. Protein production required for normal cell function is tightly linked to ribosome abundance. It is well known that ribosomal genes are actively transcribed and ribosomal messenger RNAs (mRNAs) are rapidly translated, and yet ribosomal proteins have relatively long half-lives. These observations raise questions as to how homeostasis of ribosomal proteins is controlled. Here, we show that ribosomal proteins, while posttranslationally stable, are subject to high-level cotranslational protein degradation (CTPD) except for those synthesized as ubiquitin (Ub) fusion precursors. The N-terminal Ub moiety protects fused ribosomal proteins from CTPD. We further demonstrate that cotranslational folding efficiency and expression level are two critical factors determining CTPD of ribosomal proteins. Different from canonical posttranslational degradation, we found that CTPD of all the ribosomal proteins tested in this study does not require prior ubiquitylation. This work provides insights into the regulation of ribosomal protein homeostasis and furthers our understanding of the mechanism and biological significance of CTPD.


Tetrandrine (TET) Induces Death Receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5) and Sensitizes Prostate Cancer Cells to TRAIL-Induced Apoptosis.
TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells, but not in normal cells; as such, it is a promising therapeutic agent. However, therapeutic resistance limits its clinical use in many malignancies, including prostate cancer. Strategies to sensitize cancer cells to TRAIL are urgently needed. We demonstrate here that small-molecule tetrandrine (TET) potentially sensitizes previously resistant (LNCaP and C4-2B cells) and mildly sensitive (PC3 cells) prostate cancer cells to TRAIL-induced apoptosis, and they do so by upregulating mRNA expression and protein levels of death receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5). Using shRNA knockdown, we show critical requirement of DR4 and DR5 in sensitization of prostate cancer cells to TRAIL. We show that double knockdown of DR4 and DR5 abrogated the apoptotic effects of TET and TRAIL. We also demonstrate that TET-induced DR4 and DR5 expression is independent of p53 status. Given that loss of p53 is associated with progression of prostate cancer to CRPC and NEPC, our results show that TET, by acting as a TRAIL-sensitizing agent in prostate cancer, could serve as a potential therapeutic agent in CRPC and NEPC, for which there is no cure to date. Mol Cancer Ther; 17(6); 1217-28. ©2018 AACR.


Observation of e^{+}e^{-}→ωχ_{bJ}(1P) and Search for X_{b}→ωϒ(1S) at sqrt[s] near 10.75 GeV.
We study the processes e^{+}e^{-}→ωχ_{bJ}(1P) (J=0, 1, or 2) using samples at center-of-mass energies sqrt[s]=10.701, 10.745, and 10.805 GeV, corresponding to 1.6, 9.8, and 4.7 fb^{-1} of integrated luminosity, respectively. These data were collected with the Belle II detector during special operations of the SuperKEKB collider above the ϒ(4S) resonance. We report the first observation of ωχ_{bJ}(1P) signals at sqrt[s]=10.745 GeV. By combining Belle II data with Belle results at sqrt[s]=10.867 GeV, we find energy dependencies of the Born cross sections for e^{+}e^{-}→ωχ_{b1,b2}(1P) to be consistent with the shape of the ϒ(10753) state. These data indicate that the internal structures of the ϒ(10753) and ϒ(10860) states may differ. Including data at sqrt[s]=10.653 GeV, we also search for the bottomonium equivalent of the X(3872) state decaying into ωϒ(1S). No significant signal is observed for masses between 10.45 and 10.65 GeV/c^{2}.


[From malaria parasite point of view--Plasmodium falciparum evolution].
Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium, which have arguably exerted the greatest selection pressure on humans in the history of our species. Besides humans, different Plasmodium parasites infect a wide range of animal hosts, from marine invertebrates to primates. On the other hand, individual Plasmodium species show high host specificity. The extraordinary evolution of Plasmodium probably began when a free-living red algae turned parasitic, and culminated with its ability to thrive inside a human red blood cell. Studies on the African apes generated new data on the evolution of malaria parasites in general and the deadliest human-specific species, Plasmodium falciparum, in particular. Initially, it was hypothesized that P. falciparum descended from the chimpanzee malaria parasite P. reichenowi, after the human and the chimp lineage diverged about 6 million years ago. However, a recently identified new species infecting gorillas, unexpectedly showed similarity to P. falciparum and was therefore named P. praefalciparum. That finding spurred an alternative hypothesis, which proposes that P. falciparum descended from its gorilla rather than chimp counterpart. In addition, the gorilla-to-human host shift may have occurred more recently (about 10 thousand years ago) than the theoretical P. falciparum-P. reichenowi split. One of the key aims of the studies on Plasmodium evolution is to elucidate the mechanisms that allow the incessant host shifting and retaining the host specificity, especially in the case of human-specific species. Thorough understanding of these phenomena will be necessary to design effective malaria treatment and prevention strategies.


Jasmonic acid protects etiolated seedlings of Arabidopsis thaliana against herbivorous arthropods.
Seed predators can cause mass ingestion of larger seed populations. As well, herbivorous arthropods attempt to attack etiolated seedlings and chose the apical hook for ingestion, aimed at dropping the cotyledons for later consumption. Etiolated seedlings, as we show here, have established an efficient mechanism of protecting their Achilles' heel against these predators, however. Evidence is provided for a role of jasmonic acid (JA) in this largely uncharacterized plant-herbivore interaction during skotomorphogenesis and that this comprises the temporally and spatially tightly controlled synthesis of a cysteine protease inhibitors of the Kunitz family. Interestingly, the same Kunitz protease inhibitor was found to be expressed in flowers of Arabidopsis where endogenous JA levels are high for fertility. Because both the apical hook and inflorescences were preferred isopod targets in JA-deficient plants that could be rescued by exogenously administered JA, our data identify a JA-dependent mechanism of plant arthropod deterrence that is recalled in different organs and at quite different times of plant development.


Analysis of NF-kappaB signaling pathways by proteomic approaches.
NF-kappaB is a transcription factor that plays important roles in the regulation of apoptosis and inflammation as well as innate and adaptive immunity. Consequently, dysregulations in the NF-kappaB activation cascade have been associated with the pathogenesis of several diseases such as cancer, atherosclerosis and rheumatoid arthritis. Although NF-kappaB signaling pathways have been extensively investigated in this context, its varying components and targets are far from being completely elucidated. There is still an urgent need for the detection of novel NF-kappaB target proteins, novel interaction partners and novel regulators in the activation cascade, in particular with regard to its role in the aforementioned diseases. Therefore, several groups have performed different proteomic approaches to further investigate NF-kappaB signal transduction pathways. Most of these studies have been carried out in the area of cancer research; however, there are also several analyses in the field of inflammatory or autoimmune diseases. Furthermore, there have been a number of basic investigations that principally examined binding partners or so far unknown target proteins of NF-kappaB-related proteins. With these approaches, a number of novel and interesting proteins have been found that interfere with NF-kappaB signal transduction and might have an impact on NF-kappaB-related diseases. The results of these studies are summarized and discussed in this review.


A laboratory comparison of the efficacy of battery-operated, non-rechargeable power toothbrushes.
To evaluate the cleaning efficacy of three battery-operated, non-rechargeable, oscillating/rotating power toothbrushes, using a robot system to simulate normal clinical toothbrush use. The study compared the cleaning efficacy of the new Braun Oral-B D4/EB4 with the Actibrush and the Dr. Best Powerclean in two independent experiments. Plaque substitute was applied to the artificial teeth of typodonts, which were cleaned by the robot system for a total of 2 minutes at a brushing force of 1.95 N. The remaining plaque substitute on buccal + lingual/palatal and occlusal surfaces, as well as gingival margin and interproximal sites, was measured using a computerized vision system. The new D4/EB4 was found to remove more plaque substitute than the Actibrush at all sites, and for all surfaces, lingual surfaces and occlusal surfaces the difference in favor of the D4/EB4 was statistically significant (P < 0.05). In comparison with the Powerclean toothbrush, the D4/EB4 was significantly more effective at all sites (P < 0.001). These results indicate that not all battery-operated oscillating/rotating power toothbrushes have equal efficacy with respect to plaque removal and that, in this series of laboratory experiments, the Braun Oral-B D4/EB4 was more effective than the Actibrush and the Dr. Best Powerclean.


Critical behavior in broad-band dielectric relaxation on approaching the critical consolute point in ethanol-dodecane mixture.
We present a quantitative experimental evidence for the influence of critical fluctuations on the high frequency dielectric relaxation in a binary critical mixture. The analysis clearly shows the presence of critical anomaly both for the maxima (epsilon(")(p)) and frequencies (f(p)) of loss curves peaks. For the temperature evolution of epsilon(")(p) similar relation as for the static dielectric permittivity was obtained. The temperature dependence of relaxation times can be portrayed by using the Eyring-type equation remote from the critical consolute point and shows the unusual precritical speeding up. The obtained behavior resembles that found recently in the isotropic phase of nematic liquid crystals [A. Drozd-Rzoska and S. J. Rzoska, Phys. Rev. E 65, 041701 (2002)]. Results presented agree also with the recent theoretical suggestion [S. Goodyear and S. C. Tucker, J. Chem. Phys. 111, 9673 (1999)] that relaxation in supercritical fluids may exhibit glasslike features.


Calcium channel blockers in organ transplantation: important new therapeutic modalities.
The calcium channel blockers have emerged as important therapeutic modalities in the treatment of hypertension, ischemic heart disease, and other cardiovascular diseases. More recently, their potential benefit in recipients of organ transplants has come under closer scrutiny. Calcium channel blockers depress in vitro cellular immunity in an additive fashion with cyclosporine and have been demonstrated to reduce the incidence of rejection posttransplantation in early clinical trials. This class of drugs may also diminish ischemic damage to transplanted organs and reduce the destructive aspects of reperfusion injury. Because of their ability to depress cellular immune responses to mitogens, calcium channel blockers may also prove useful in decreasing the incidence of first-dose side effects (related to lymphocyte stimulation) in response to treatment with the OKT3 monoclonal antibody, a commonly used antirejection medication. Recent investigative efforts also suggest that calcium channel blockers may minimize cyclosporine nephrotoxicity by antagonizing either the direct or indirect vasoconstrictive actions of the drug. Some of the calcium channel blockers also reduce cyclosporine metabolism and excretion, thus allowing adequate levels of cyclosporine in blood with reduced doses of this valuable immunosuppressive agent. Cyclosporine-treated renal transplant recipients are frequently hypertensive, which is likely related to a salt-sensitive physiology. Calcium channel blockers have demonstrated important efficacy in reducing blood pressure in low-renin, salt-sensitive patients and similarly have been efficacious in controlling blood pressure in cyclosporine-treated transplant recipients. The numerous potential applications of calcium channel blockers in the field of organ transplantation illustrates the need for expanded clinical trials evaluating their use in this area.


Public communication, risk perception, and the viability of preventive vaccination against communicable diseases.
Because of the nature of preventive vaccination programs, the viability of these public health interventions is particularly susceptible to public perceptions. This is because vaccination relies on a concept of 'herd immunity', achievement of which requires rational public behavior that can only be obtained through full and accurate communication about risks and benefits. This paper describes how irrational behavior that threatens the effectiveness of vaccination programs--both in crisis and non-crisis situations--can be tied to public perceptions created by media portrayals of health risks. I concentrate on childhood vaccination as an exemplar of 'non-crisis' preventive vaccination, and on the recent flu vaccine shortage as a 'crisis' situation. The paper concludes with an examination of the steps necessary to resolve these threats through better public communication.


A Novel Designed Valved Conduit for RVOT Reconstruction in Grown-up Congenital Heart Patients: a Glimpse Down the Road.
A plethora of valves and valve conduits are available for reconstruction of the right ventricular outflow tract (RVOT) for grown-up congenital heart patients. However, for several reasons, the ideal pulmonary valve substitute still remains the subject of debate. In this study, we investigated the preliminary clinical and echocardiographic results after implantation of the RVOT Elan (Vascutek, Renfrewshire, United Kingdom) conduit in adolescents and adults. Between October 2012 and December 2014, a total of 27 patients (19 males, mean age: 23.7 ± 22.5; range: 9-74 years) received a RVOT Elan conduit for RVOT reconstruction and were prospectively followed up clinically and echocardiographically. Twenty-five patients had previous cardiac surgery. The median number of prior operations per patient was 2 (range: 1-4). Tetralogy of Fallot was the most common diagnosis (n = 7). At a mean follow-up time of 0.9 ± 0.61 years (100% complete), all patients (27 of 27) were alive and in New York Heart Association Class I. Adverse events defined as valve failure, thrombosis, embolism, bleeding, or endocarditis did not occur. Freedom from reoperation in general was 100%. At 1-year follow-up, median peak pressure gradients (Δ Pmax) across the RVOT Elan conduit were 15 ± 3.2; 15.3 ± 2.1Δ, 16 ± 4.8, and 16.3 ± 5.1 mm Hg for the 19 (n = 3), 21 (n = 3), 23 (n = 6), and 25 mm (n = 15) conduit size, respectively. The RVOT Elan conduit revealed excellent preliminary clinical and hemodynamic performances independent from the underlying cardiac pathology with insignificant transvalvular gradients and nonturbulent flow characteristics.


Cardiolipotoxicity, Inflammation, and Arrhythmias: Role for Interleukin-6 Molecular Mechanisms.
Fatty acid infiltration of the myocardium, acquired in metabolic disorders (obesity, type-2 diabetes, insulin resistance, and hyperglycemia) is critically associated with the development of lipotoxic cardiomyopathy. According to a recent Presidential Advisory from the American Heart Association published in 2017, the current average dietary intake of saturated free-fatty acid (SFFA) in the US is 11-12%, which is significantly above the recommended <10%. Increased levels of circulating SFFAs (or lipotoxicity) may represent an unappreciated link that underlies increased vulnerability to cardiac dysfunction. Thus, an important objective is to identify novel targets that will inform pharmacological and genetic interventions for cardiomyopathies acquired through excessive consumption of diets rich in SFFAs. However, the molecular mechanisms involved are poorly understood. The increasing epidemic of metabolic disorders strongly implies an undeniable and critical need to further investigate SFFA mechanisms. A rapidly emerging and promising target for modulation by lipotoxicity is cytokine secretion and activation of pro-inflammatory signaling pathways. This objective can be advanced through fundamental mechanisms of cardiac electrical remodeling. In this review, we discuss cardiac ion channel modulation by SFFAs. We further highlight the contribution of downstream signaling pathways involving toll-like receptors and pathological increases in pro-inflammatory cytokines. Our expectation is that if we understand pathological remodeling of major cardiac ion channels from a perspective of lipotoxicity and inflammation, we may be able to develop safer and more effective therapies that will be beneficial to patients.


Are Limits of Concern a useful concept to improve the environmental risk assessment of GM plants?
The European Food Safety Authority (EFSA) has introduced a concept for the environmental risk assessment of genetically modified (GM) plants which foresees the definition of ecological threshold values defining acceptable adverse effects of the GM plant on the environment (Limits of Concern, LoC). We analysed the LoC concept by scrutinising its feasibility with regard to important aspects of the environmental risk assessment. We then considered its relationship with protection goals, the comparative safety assessment and the stepwise testing approach. We finally discussed its usefulness for assessing long-term effects, effects on non-target organisms and species of conservation concern. The LoC concept is a possible approach to introduce ecological thresholds into environmental risk assessment in order to evaluate environmental harm. However, the concept leaves many important aspects open. Thresholds for environmental harm for protection goals need spatial and temporal differentiation from LoCs used for ERA indicators. Regionalisation of LoCs must be provided for as biodiversity levels and protection goals vary across the EU. Further guidance is needed with respect to the consequences, in case LoCs are exceeded and a link needs to be established between environmentally relevant results from the comparative safety assessment and the LoC concept. LoCs for long-term effects have to be evaluated by long-term monitoring. LoCs for non-target organisms need to be discriminated according to the species and parameters assessed. The overall LoC concept is considered useful if LoCs are further specified and differentiated. Although LoCs will finally be determined by political decisions, they should be based on scientific grounds in order to increase confidence in the conclusions on the safety of GM plants.


Ischemia-induced structural change in SR Ca2+-ATPase is associated with reduced enzyme activity in rat muscle.
In this study, we employed an in vivo model of prolonged ischemia in rat skeletal muscle to investigate the hypothesis that structural modifications to the sarcoplasmic reticulum (SR) Ca2+-ATPase can explain the alterations in Ca2+-ATPase activity that occur with ischemia. To induce total ischemia, a tourniquet was placed around the upper hindlimb in 27 female Sprague-Dawley rats weighing 256 +/- 6.7 g (mean +/- SE) and was inflated to 350 mmHg for 4 h. The contralateral limb served as control (C) to the ischemic limb (I), and the limbs of animals killed immediately after anesthetization served as a double control (CC). Mixed gastrocnemius and tibialis anterior muscles were sampled and used for SR vesicle preparation. Maximal Ca2+-ATPase activity (micromol x g protein(-1) x min(-1)) of C (15,802 +/- 1,246) and I (11,609 +/- 1,029) was 90 and 73% (P < 0.05) of CC (17,562 +/- 1,682), respectively. No differences were found between groups in either the Hill coefficient or the free Ca2+ at half-maximal activity. The fluorescent probes, FITC and N-cyclohexyl-N'-(dimethylamino-alpha-naphthyl) carbodiimide, used to assess structural alterations in the regions of the ATP binding site and the Ca2+ binding sites of the Ca2+-ATPase, respectively, indicated a 26% reduction (P < 0.05) in FITC binding capacity (absolute units) in I (0.22 +/- 0.01) compared with CC (0.29 +/- 0.02) and C (0.29 +/- 0.03). Our results suggest that the reduction in maximal SR Ca2+-ATPase activity in SR vesicles with ischemia is related to structural modification in the region of the nucleotide binding domain by mechanisms that are as yet unclear.


Preventing abuse of older people.
The author travelled to the United States on a Florence Nightingale Travel Scholarship to study the systems in place to respond to and prevent elder abuse. She visited centres in Orange County, California, and New York City that are involved in dealing with the issue. This article provides a summary of her findings, with emphasis on education and training strategies for healthcare professionals working with older people, and provides recommendations for developments in safeguarding older people in the UK. The author also reviews models of service, models of evaluation and approaches to older people who self-neglect.


The protective role of epidermal melanin in a patient with porphyria variegata and vitiligo.
To assess the role of epidermal melanin in a patient with porphyria variegata and vitiligo, the MED was determined in pigmented and vitiliginous skin for wavelengths of 310, 405 and 500 nm. The energy required to elicit erythema by irradiating vitiliginous skin at 310 nm was half that for pigmented skin. For 405 nm the differences was 4-fold and at 500 nm 2-fold. A possible explanation for the different protection by melanin against light of 310, 405 and 500 nm is given. UV-B irradiation, as a potent stimulus for melanization of the skin, is proposed as an additive measure in the protection against photosensitivity reactions in porphyria patients.


Aortoenteric fistula: a late complication of endovascular repair of an inflammatory abdominal aortic aneurysm.
Endovascular repair provides a reasonable alternative to open repair for the treatment of abdominal aortic aneurysms in select cases. Although the endovascular approach may be preferable for inflammatory aneurysms, aggressive surveillance is needed to monitor for long-term complications. A 61-year-old man underwent endovascular exclusion of a symptomatic inflammatory abdominal aortic aneurysm with an AneuRx bifurcated aortic prosthesis. He presented with gastrointestinal bleeding 51/2 months later and was found to have an aortoenteric fistula involving the third portion of the duodenum. The aneurysm had expanded significantly at the proximal neck. The patient underwent successful removal of the device, aortic ligation, and extraanatomic bypass. Aortoenteric fistula is a rare but now established complication of endovascular aneurysm repair. The pathophysiology in these cases remains unclear. The presence of inflammation and endoleak may predispose to further aneurysmal degeneration.


Binding of fatty acids to beta-cryptogein: quantitative structure-activity relationships and design of selective protein mutants.
Binding of fatty acids to cryptogein, the proteinaceous elicitor from Phytophthora, was studied by using molecular docking and quantitative structure-activity relationships analysis. Fatty acids bind to the groove located inside the cavity of cryptogein. The structure-activity model was constructed for the set of 27 different saturated and unsaturated fatty acids explaining 87% (81% cross-validated) of the quantitative variance in their binding affinity. The difference in binding between saturated and unsaturated fatty acids was described in the model by three electronic descriptors: the energy of the lowest unoccupied molecular orbital, the energy of the highest occupied molecular orbital, and the heat of formation. The presence of double bonds in the ligand generally resulted in stronger binding. The difference in binding within the group of saturated fatty acids was explained by two steric descriptors, i.e., ellipsoidal volume and inertia moment of length, and one hydrophobicity descriptor, i.e., lipophility. The developed model predicted strong binding for two biologically important molecules, geranylgeranyol and farnesol playing an important role in plant signaling as lipid anchors of some membrane proteins. Elicitin mutants selectively binding only one type of ligand were designed for future experimental studies.


[Analysis of the principle of lever about adjustment of spinal "Gucuofeng" with manipulative maneuver].
Spinal "Gucuofeng" mainly is considered as abnormalities of joint function. Manipulative maneuver have obviously effect in adjustment of spinal "Gucuofeng", and the technical key point is utilization of principle of lever to achieve safe, effective and labor-saving purpose. After clinical practice, the general principle of manipulative maneuver in adjustment of spinal "Gucuofeng" can be summed up as pull stretch traction, first-induced instability, reverse adjustment,withdraw along situation.


Immunohistochemical detection of the hMLH1 and hMSH2 proteins in hereditary non-polyposis colon cancer and sporadic colon cancer.
Defects in DNA mismatch repair system are involved in carcinogenesis of sporadic and inherited human cancers. We assessed the feasibility of using immunohistochemistry to detect tumors with DNA mismatch repair deficiency. We analyzed 81 samples (74 colon cancers (CC), 1 colon dysplasia and 6 extracolonic cancers) for hMLH1 and hMSH2 protein expression, microsatellite instability (MSI) and/or mutational analysis. A meta-analysis of the published data on immunohistochemistry of hMLH1/hMSH2 proteins was performed. Sensitivity and specificity of the method was calculated. Twenty four of 29 tumors from hMLH1/hMSH2 mutation carriers and 10 of 13 sporadic high frequency MSI tumors lost one of the proteins. None of the 42 tumors with stable microsatellites or low frequency MSI lost the proteins. Based on literature review of 49 publications on colorectal cancer, hMLH1 immunohistochemistry was able to detect 136 of 154 tumors from hMLH1 germline mutation carriers (the sensitivity of 88.3% [95%CI, 85.8-90.8%]), hMSH2 immunohistochemistry detected 99 of 109 tumors from hMSH2 mutation carriers (the sensitivity of 90.8% [95%CI, 88.5-93.1%]), and hMLH1/hMSH2 immunohistochemistry identified 1262 of 1382 tumors with high-frequency microsatellite instability not correlated with mutational analysis (the sensitivity of 91.3% [95%CI, 90.4-92.2%]). The specificity of the method was 99.4% (95%CI, 99.2-99.6%). In conclusion, immunohistochemistry of hMLH1 and hMSH2 proteins is a useful method to predict the presence of mismatch repair deficiency, although its sensitivity is lower than that of MSI analysis.


US payer perspectives on evidence for formulary decision making.
The perspective of commercial payers on comparative effectiveness research (CER) has not been well researched. This study aims to describe how US commercial payers use and value CER for formulary decision making in different disease states. We recruited 20 medical and pharmaceutical directors from national and regional plans who are involved in pharmaceutical and therapeutics committees to participate in the study. We conducted in-depth qualitative interviews with the payers and asked them to rate the usefulness of CER study types across various disease states and market conditions. The results were analyzed for thematic content. Our findings indicate that payers are interested in a broad range of CER study types, are unsatisfied with the current state of CER, and would like to partner with research groups to develop research and treatment guidelines to better leverage CER. Payers value CER less in oncology than in other disease states because of limitations in their ability to manage oncology therapies. To improve formulary design processes and support payers in providing more effective healthcare, policy makers should consider involving commercial payers in the development of CER as well as in the creation of research and treatment guidelines.


Expression of Pain Behaviors and Perceived Partner Responses in Individuals With Chronic Pain: The Mediating Role of Partner Burden and Relationship Quality.
Expressions of pain by individuals with chronic pain may encourage solicitous and distracting responses from some partners and punishing responses from others. Partners' responses can impact the well-being of individuals with chronic pain. Yet information about factors that can explain the link between expression of pain behaviors and different partners' responses is scarce. The objective of this study was to investigate the role of perceived partner burden and relationship quality in the link between expressions of pain behaviors and perceived partner responses (ie, solicitous, distracting, and punishing responses). Participants were 158 individuals with chronic pain (ie, experiencing pain on most days for at least 6 months before participating in the study) who completed questionnaires about pain behaviors, as well as perceptions of partner burden, relationship quality, and partners' solicitous, distracting, and punishing responses. The link between expressing pain and each type of partner response was investigated by serial mediation analysis. Partner burden and relationship quality were entered into all analyses as the first and the second mediator, respectively. Expressing more pain was related to higher levels of perceived partner burden, which in turn, was associated with poorer relationship quality. Poorer relationship quality was associated with reporting fewer solicitous and distracting partner responses and more punishing responses. Enhanced partner burden and reduced relationship quality may be one pathway through which pain behaviors relate to partner responses.


Issue network versus producer network? ASH, the Tobacco Products Research Trust and UK smoking policy.
Policy science studies of networks in smoking policy segment the smoking arena into a "producer network" of industrial and retail interests and an "issue network" of anti-smoking organisations. Case studies of ASH (Action on Smoking and Health) and the Tobacco Products Research Trust (TPRT) indicate that networks in smoking policy were more complex and overlapping. ASH pioneered a new style of media-conscious health activism in the 1970s with an anti-industry line. Nevertheless the strategy of harm reduction remained an objective for industry and government, and also for some public health interests through the work of the TPRT. First safer smoking and then nicotine were the focus of these activities.


Multibiomarker interactions to diagnose and follow-up chronic exposure of a marine crustacean to Hazardous and Noxious Substances (HNS).
Integrated compensatory responses of physiological systems towards homeostasis are generally overlooked when it comes to analysing alterations in biochemical parameters indicative of such processes. Here an hypothesis-driven multivariate analysis accounting for interactive multibiomarker responses was used to investigate effects of long-term exposure of Carcinus maenas to Hazardous and Noxious Substances (HNS). Adult male crabs were exposed to low and high post-spill levels of acrylonitrile (ACN) or aniline (ANL) for 21d. Bioaccumulation, feeding behaviour, and biomarkers related to mode-of-action (MoA) (detoxification, neurotransmission and energy production) were evaluated over time. Distinct temporal patterns of response to low and high exposure concentrations were depicted, with a main set of interactive multibiomarker predictors identified for each HNS (five for ACN and three for ANL), useful to follow coupled evolvement of biomarker responses. ACN caused peripheral neurotoxic effects coupled with enhanced biotransformation and significant oxidative damage particularly relevant in gills. ANL elicited alterations in central neurotransmission affecting ventilation coupled with very low levels of oxidative damage in gills. Results indicate chronic toxicity data are determinant to improve HNS hazard assessment if the aim is to obtain reliable risk calculations, and develop effective predictive models avoiding overestimation but sufficiently protective. Accounting for multibiomarker interactions brought otherwise overlooked information about C. maenas responses and MoA of ACN and ANL.


[Application of quality constant method in grade evaluation of Aurantii Fructus Immaturus pieces].
The grade classification of Chinese herbal medicines and their decoction pieces has always been a hot issue in the industry. In the trading history of Chinese herbal medicine,buyers and sellers often determine the price according to quality,so the naturally formed specifications and grades are changing with the change of technology and the increasing demand of the public for medical care.The planting,processing and circulation methods of Chinese medicinal materials have also changed greatly. Under the mode of pursuing yield and short-term benefit,the traditional rating evaluation method has been difficult to be used in the current quality status of prepared slices. Aurantii Fructus Immaturus is a genuine medicinal material of Jiangxi province,which is widely used,but has different quality levels on the market. In this paper,the quality levels were evaluated by the mass constant method. A set of grading method of Aurantii Fructus Immaturus slices was established,laying a foundation for " high quality and high price" Aurantii Fructus Immaturus slices. The grading method of Chinese herbal slices with quality constant was applied to 16 batches of Aurantii Fructus Immaturus slices collected form the market,and the final assessment results were as follows for different piece shapes( hemispherical type and thin type)respectively. The hemispherical Aurantii Fructus Immaturus pieces: quality constant ≥1. 11 for the first grade,< 1. 11 but ≥0. 69 for the second grade,and <0. 69 for the third grade. The thin type Aurantii Fructus Immaturus pieces: quality constant ≥0. 024 for the first grade,<0. 024 but ≥0. 015 for the second grade,and <0. 015 for the third grade. This work indicated that the quality constants grading method can be used to objectively classify the grades of traditional Chinese medicine,providing basis for standardizing market behavior and providing useful reference for grading of hemispherical or thin Aurantii Fructus Immaturus pieces.


Eo na Mahu o Hawai'i: the extraordinary health needs of Hawai'i's Mahu.
An overview of health and social issues is presented here regarding Native Hawaiian transgenders. Perhaps due to relatively greater tolerance of gender diversity among Polynesian cultures, approximately 70% of all male-to-female transgenders in Hawai'i are Native Hawaiian. However, the overall climate is one of discrimination and harassment such that transgenders--who tend to be under-educated, under-employed, and medically underserved--may be the most severely impacted of all Native Hawaiians. Lei Anuenue, human immunodeficiency virus (HIV) prevention program for Native Hawaiians, has provided a variety of services for transgenders, including outreach, educational workshops, support groups, HIV testing, and case management. All services are provided by peer leaders who are employed by the program. Data for this article are based on case management, including client self-disclosures and reports of peer staff who knew details of clients' lives having shared with them both generic experiences and specific activities. Information from 100 transgender clients and their case managers indicated that the transgender health profile is far more serious than that of mainstream Native Hawaiians. For example, 74% smoke, 31% use illegal drugs (excluding marijuana), more than 50% have been involved in street or domestic violence, and few individuals over age 50 have been found during three years of outreach. To some extent, employment options limit transgenders to prostitution, drug dealing, and minimum-wage jobs. In addition, a lifestyle of multiple sex partners and lack of opportunities for stable relationships place transgenders at much greater risk for HIV, sexually transmitted diseases (STD), and other infectious and non-infectious diseases as compared to the mainstream Native Hawaiian community. Clients in this study were from O'ahu, primarily from downtown Honolulu, Chinatown, and Wai'anae. Future studies should compare the results of this sample to transgenders from the neighbor islands (especially in rural Hawaiian areas), as well as utilize a structured prospective longitudinal approach.


Sirolimus dosage during and after conversion from calcineurin inhibitor therapy to sirolimus in chronic kidney transplant patients.
Sirolimus (SRL) is an alternative to calcineurin inhibitors (CNI) in kidney transplant patients with chronic allograft dysfunction. 33 patients were converted to SRL receiving a single loading dose of 15 mg and initial maintenance dose of 5 mg/day. CNI was reduced by 50% on day 1 and tapered during 4-6 weeks after achieving SRL target (8-12 ng/ml). Concomitant immunosuppressive therapy remained unchanged. Patient survival was 100% and graft survival was 85% after 1 year. Mean SRL dose decreased from 5 mg/day initially to 2.8 +/- 1.3 mg/day. SRL dose-adjusted trough concentration did not change significantly over time. Dose-adjusted trough concentrations of CNI before conversion and of SRL after 1 year did not correlate. We observed no severe infections, however, one rejection Banff Ia occurred 7 months after conversion associated with subtherapeutic SRL trough concentration. Adverse events were anemia, dyslipidemia, epistaxis, stomatitis, and bronchiolitis obliterans which occurred mainly during the conversion phase. Overlapping conversion from CNI to SRL in chronic kidney transplant patients is possible and safe. However, further studies are necessary with shorter overlap and lower SRL loading and initial maintenance dose which might lead to a decrease in the high number of adverse events in the overlap phase.


Melanoma in Hispanic and black Americans.
Although age-adjusted incidence rates (per 100,000) for melanoma are lower among Hispanics and blacks (4.5 and 1.0, respectively) compared with white non-Hispanics (21.6), melanomas among minority populations in the United States are more likely to metastasize and have poorer outcomes. A review of the literature was conducted on melanomas affecting Hispanic and black Americans. Because of the low index of suspicion in both the medical community and these ethnic populations, diagnosis is often delayed, resulting in advanced presentation and a poorer prognosis. More comprehensive medical training, expanded public educational campaigns, and increased awareness among patients of all skin types to perform self skin checks are recommended. Further studies elucidating the etiology and risk factors for melanoma among minority populations are warranted.


Total hip replacement: A meta-analysis to evaluate survival of cemented, cementless and hybrid implants.
To determine whether cemented, cementless, or hybrid implant was superior to the other in terms of survival rate. Systematic searches across MEDLINE, CINAHL, and Cochrane that compared cemented, cementless and hybrid total hip replacement (THR) were performed. Two independent reviewers evaluated the risk ratios of revision due to any cause, aseptic loosening, infection, and dislocation rate of each implants with a pre-determined form. The risk ratios were pooled separately for clinical trials, cohorts and registers before pooled altogether using fixed-effect model. Meta-regressions were performed to identify the source of heterogeneity. Funnel plots were analyzed. Twenty-seven studies comprising 5 clinical trials, 9 cohorts, and 13 registers fulfilled the research criteria and analyzed. Compared to cementless THR, cemented THR have pooled RR of 0.47 (95%CI: 0.45-0.48), 0.9 (0.84-0.95), 1.29 (1.06-1.57) and 0.69 (0.6-0.79) for revision due to any reason, revision due to aseptic loosening, revision due to infection, and dislocation respectively. Compared to hybrid THR, the pooled RRs of cemented THR were 0.82 (0.76-0.89), 2.65 (1.14-6.17), 0.98 (0.7-1.38), and 0.67 (0.57-0.79) respectively. Compared to hybrid THR, cementless THR had RRs of 0.7 (0.65-0.75), 0.85 (0.49-1.5), 1.47 (0.93-2.34) and 1.13 (0.98-1.3). Despite the limitations in this study, there was some tendency that cemented fixation was still superior than other types of fixation in terms of implant survival.


Accommodative Anomalies in a Sample of Black High School Students in South Africa.
Accommodative anomalies cause asthenopia and affect student reading efficiency and academic performance. The aim of conducting this study was to determine the prevalence and distribution of accommodative anomalies (insufficiency, excess and infacility) in relation to demographic variables (sex, age, school grade level and study location). Study participants comprised 1,211 children (481 male and 730 female), with age range 13-19 years. Visual functions evaluated included refractive error, accommodative amplitude, accuracy, facility and relative accommodation. A total of 242 participants (20.2%) had accommodative anomalies. Prevalence estimates were; accommodative infacility 12.9% (95% confidence interval, CI, 10.9-14.7%), accommodative insufficiency 4.5% (95% CI 3.4-5.8%) and accommodative excess 2.8% (95% CI 1.9-3.8%). There were no significant differences based on sex, school grade level or study site, except in the prevalence of accommodative infacility, which was significantly higher in the younger grade level than the older (P=0.027). The study fills a gap in the literature in providing data on predominantly black South African students. The prevalence estimates for accommodative insufficiency and excess found in the sample studied are relatively low, while that of accommodative infacility is high. Accommodative anomalies were not markedly associated with demographic variables except for the prevalence of accommodative infacility, which was significantly higher in the younger grade level than the older. Identification and referral are important steps towards diagnosis and treatment of accommodative anomalies. Future studies on differences in prevalence of accommodative anomalies among different racial populations will be relevant.


Three New Lactobacillus plantarum Strains in the Probiotic Toolbox against Gut Pathogen Salmonella enterica Serotype Typhimurium.
The benefits of probiotic bacteria have been widely explored. However, fermented foods and digestive system of humans and animals are an inexhaustible source of new potentially probiotic microorganisms. In this study we present three new Lactobacillus plantarum strains isolated from different dairy products: cow's cheese, sheep's cheese and whey. In order to determine the antibacterial activity of yet unexplored L. plantarum strains against Salmonella enterica serotype Typhimurium, in vitro competition and co-culture tests were done. Furthermore, adhesion of these strains to Caco-2 cells and their influence on the adhesion of Salmonella were tested. Results showed the potential probiotic activity of isolated strains. L. plantarum strains survived in the presence of 1% bile salts, they possessed acidification ability, antibacterial activity and significantly attenuated the growth of S. Typhimurium in brain heart infusion broth. All tested L. plantarum strains were able to adhere to Caco-2 cells and significantly impair the adhesion of S. Typhimurium. All three L. plantarum strains exhibited significant probiotic potential and anti-Salmonella activity; therefore, further testing on in vivo models should follow.


Composite integron array generated by insertion of an ORF341-type integron within a Tn21-like element.
Two class 1 integrons, In-t1 and In-t2, were previously identified in IncFI plasmids of Salmonella enterica serotype Typhimurium. Molecular analysis revealed a close physical link between the two integrons. In-t1 is preceded by the transposase genes of Tn21, whereas In-t2 is located downstream the 3'-conserved segment (3'-CS) of In-t1, in a head-to-tail configuration. In-t1 shows a peculiar sequence downstream the 3'-CS, containing an extended version of the open reading frame known as ORF341 (referred to as ORF341E) and a novel trimethoprim resistance gene, designated dfrA18. Retrospective analysis provided evidence for In-t1 insertion within Tn1935, a Tn21-related transposon identified in IncFI plasmids circulating among epidemic clones of multidrug-resistant S. enterica during the 1970s. Structural comparison between Tn21 derivatives from recent and ancestor IncFI plasmids showed that In-t2 has been conserved by these replicons. In-t1 belongs to a novel family of class 1 integrons containing the ORF341E sequence, and appears to have been acquired by IncFI plasmids after the assembly of Tn1935. In-t1 insertion occurred within the 5'-conserved segment (5'-CS) proximal region of the resident In-t2.


"Paintings Fade Like Flowers": Pigment Analysis and Digital Reconstruction of a Faded Pink Lake Pigment in Vincent van Gogh's Undergrowth with Two Figures.
Color fading in Vincent van Gogh's Undergrowth with Two Figures was studied chemically to facilitate the creation of a digital reconstruction of fugitive colors . The painting contains a field of white, green, orange, and yellow flowers under a canopy of poplar trees with two central figures-a man and a woman, arms entwined. From Van Gogh's letters, however, it is known that he painted the picture with some pink flowers, which appear to have altered, presumably to white. Raman spectroscopy was applied to microsamples of paint to identify the faded pigment as geranium lake, which in this painting consists of the dye, eosin (2',4',5',7'-tetrabromofluorescein). For the first time, lead(II) sulfate has been specifically identified as the likely inorganic substrate for a geranium lake used by Van Gogh in the last months of his life. Microfocus X-ray fluorescence (MXRF) spectroscopy was subsequently used in situ to analyze the white flowers to identify bromine as a proxy for eosin, thus indicating an original pink coloration. Of the 387 white flowers analyzed, 37.7% contained measurable bromine and were, therefore, originally pink. Several cross-sections from these formerly pink areas were assessed using a combination of visual inspection and microcolorimetry to create a colored mask in Adobe Photoshop to digitally reconstruct a suggestion of the original appearance of the painting with regard to the faded flowers. Additionally, microfadeometry was undertaken for the first time on a painting cross-section sample to understand the actual fading kinetics of the underlying bright pink geranium lake used by Van Gogh. A combination of Raman microspectroscopy, MXRF, and scanning electron microscopy energy dispersive spectroscopy (SEM-EDS) were utilized in situ and on paint microsamples to identify the complete palette used to create Undergrowth with Two Figures.


Intermittent ventricular bigeminy as an expression of two-level Wenckebach periodicity in the reentrant pathway of extrasystoles.
A patient with intermittent ventricular bigeminy is reported in whom the presence of two-level Wenckebach periodicity in the reentrant pathway of extra-systoles is suggested. When sinus arrest was caused by vagal stimulation, no ectopic QRS complex occurred. This indicated that ventricular bigeminy was not parasystolic bigeminy but ordinary extrasystolic bigeminy. Observations of the electrocardiogram suggested that Wenckebach block occurred at two different levels in the reentrant pathway of ventricular extrasystoles. When extrasystoles were noninterpolated, Wenckebach block occurred at the distal level of the pathway and caused termination of ventricular bigeminy. On the other hand, when extrasystoles were interpolated, Wenckebach block occurred at the proximal level of the pathway. This is the first report to suggest the presence of two-level Wenckebach periodicity in a reentrant pathway of extrasystoles.


Molybdenum Oxide Nitrides of the Mo2(O,N,□)5 Type: On the Way to Mo2O5.
Blue-colored molybdenum oxide nitrides of the Mo2(O,N,□)5 type were synthesized by direct nitridation of commercially available molybdenum trioxide with a mixture of gaseous ammonia and oxygen. Chemical composition, crystal structure, and stability of the obtained and hitherto unknown compounds are studied extensively. The average oxidation state of +5 for molybdenum is proven by Mo K near-edge X-ray absorption spectroscopy; the magnetic behavior is in agreement with compounds exhibiting MoVO6 units. The new materials are stable up to ∼773 K in an inert gas atmosphere. At higher temperatures, decomposition is observed. X-ray and neutron powder diffraction, electron diffraction, and high-resolution transmission electron microscopy reveal the structure to be related to VNb9O24.9-type phases, however, with severe disorder hampering full structure determination. Still, the results demonstrate the possibility of a future synthesis of the potential binary oxide Mo2O5. On the basis of these findings, a tentative suggestion on the crystal structure of the potential compound Mo2O5, backed by electronic-structure and phonon calculations from first principles, is given.


Altered Default Mode Network on Resting-State fMRI in Children with Infantile Spasms.
Infantile spasms (IS) syndrome is an age-dependent epileptic encephalopathy, which occurs in children characterized by spasms, impaired consciousness, and hypsarrhythmia. Abnormalities in default mode network (DMN) might contribute to the loss of consciousness during seizures and cognitive deficits in children with IS. The purpose of the present study was to investigate the changes in DMN with functional connectivity (FC) and amplitude of low-frequency fluctuation (ALFF), the two methods to discover the potential neuronal underpinnings of IS. The consistency of the two calculate methods of DMN abnormalities in IS patients was also our main focus. To avoid the disturbance of interictal epileptic discharge, our testing was performed within the interictal durations without epileptic discharges. Resting-state fMRI data were collected from 13 patients with IS and 35 sex- and age-matched healthy controls. FC analysis with seed in posterior cingulate cortex (PCC) was used to compare the differences between two groups. We chose PCC as the seed region because PCC is the only node in the DMN that directly interacts with virtually all other nodes according to previous studies. Furthermore, the ALFF values within the DMN were also calculated and compared between the two groups. The FC results showed that IS patients exhibited markedly reduced connectivity between posterior seed region and other areas within DMN. In addition, part of the brain areas within the DMN showing significant difference of FC had significantly lower ALFF signal in the patient group than that in the healthy controls. The observed disruption in DMN through the two methods showed that the coherence of brain signal fluctuation in DMN during rest was broken in IS children. Neuronal functional impairment or altered integration in DMN would be one neuroimaging characteristic, which might help us to understand the underlying neural mechanism of IS. Further studies are needed to determine whether the disturbed FC and ALFF observed in the DMN are related to cognitive performance in IS patients.


Accessibility of enterobacterial common antigen to antibodies in encapsulated and non-capsulated S and R forms of Escherichia coli.
Antiserum specific for the enterobacterial 'common antigen' (ECA) was obtained by absorbing a rabbit ECA antiserum with an ECA-negative mutant. Accessibility of ECA to antibodies in encapsulated and non-capsulated S and R forms derived from Escherichia coli O8:K27 was studied using the indirect immunoferritin technique (whole-mount electron microscopy). The number of ferritin particles on the bacterial surface decreased in the order, non-capsulated R greater than encapsulated R greater than on-capsulated S greater than encapsulated S form, indicating that both the O and K antigens partly cover ECA on the surface of the outer membrane. Whole-mount and thin-section electron microscopy showed that ferritin was evenly distributed on the surface of R mutants, whereas it formed clusters on the S forms.


Three-dimensional microstructure of human alveolar trabecular bone: a micro-computed tomography study.
The microstructural characteristics of trabecular bone were identified using micro-computed tomography (micro-CT), in order to develop a potential strategy for implant surface improvement to facilitate osseointegration. Alveolar bone specimens from the cadavers of 30 humans were scanned by high-resolution micro-CT and reconstructed. Volumes of interest chosen within the jaw were classified according to Hounsfield units into 4 bone quality categories. Several structural parameters were measured and statistically analyzed. Alveolar bone specimens with D1 bone quality had significantly higher values for all structural parameters than the other bone quality categories, except for trabecular thickness (Tb.Th). The percentage of bone volume, trabecular separation (Tb.Sp), and trabecular number (Tb.N) varied significantly among bone quality categories. Tb.Sp varied markedly across the bone quality categories (D1: 0.59±0.22 mm, D4: 1.20±0.48 mm), whereas Tb.Th had similar values (D1: 0.30±0.08 mm, D4: 0.22±0.05 mm). Bone quality depended on Tb.Sp and number-that is, endosteal space architecture-rather than bone surface and Tb.Th. Regardless of bone quality, Tb.Th showed little variation. These factors should be taken into account when developing individualized implant surface topographies.


Evaluating Iowa Severe Maternal Morbidity Trends and Maternal Risk Factors: 2009-2014.
Objectives To describe statewide SMM trends in Iowa from 2009 to 2014 and identify maternal characteristics associated with SMM, overall and by age group. Methods We used 2009-2014 linked Iowa birth certificate and hospital discharge data to calculate SMM based on a 25-condition definition and 24-condition definition. The 24-condition definition parallels the 25-condition definition, but excludes blood transfusions. We calculated SMM rates for all delivery hospitalizations (N = 196,788) using ICD-9-CM diagnosis and procedure codes. We used log-binomial regression to assess the association of SMM with maternal characteristics, overall and stratified by age groupings. Results In contrast to national rates, Iowa's 25-condition SMM rate decreased from 2009 to 2014. Based on the 25-condition definition, SMM rates were significantly higher among women <20 years and >34 years compared to women 25-34 years. Blood transfusion was the most prevalent indicator, with hysterectomy and disseminated intravascular coagulation (DIC) among the top five conditions. Based on the 24-condition definition, younger women had the lowest SMM rates and older women had the highest SMM rates. SMM rates were also significantly higher among racial/ethnic minorities compared to non-Hispanic white women. Payer was the only risk factor differentially associated with SMM across age groups. First trimester prenatal care initiation was protective for SMM in all models. Conclusions High rates of blood transfusion, hysterectomy, and DIC indicate a need to focus on reducing hemorrhage in Iowa. Both younger and older women and racial/ethnic minorities are identified as high risk groups for SMM that may benefit from special consideration and focus.


Internal haemorrhoids: observations on their nature and classification in relation to their management.
Haemorrhoids become manifest as a result of enlargement and downward displacement of collections or cushions of submucosal tissue situated normally in the anal canal. The variation in the size of this tissue and the frequent lack of correlation between size and symptoms make assessment of the various forms of treatment difficult. An objective classification is outlined, together with a rational approach to treatment.


JKB-122 is effective, alone or in combination with prednisolone in Con A-induced hepatitis.
Con A-induced hepatitis in mice is an established model of autoimmune hepatitis (AIH). JKB-122, a toll-like receptor 4 (TLR4) antagonist, was tested for hepatotprotectant activity. Within several hours of Con A challenge (15mg/kg iv), increased production of proinflammatory cytokines with inflammatory infiltrate occurred in the liver. The severity of tissue necrosis and the amount of circulating liver enzymes peak at 24h post Con A challenge. JKB-122 was given 24 and 16h before, then concurrently, and 4 and 8h (× 5 doses) after challenge with Con A. Serum and liver were harvested at 3, 9 and 24h post Con A challenge. JKB-122 at 20 and 50mg/kg po prevented the increase of serum liver enzymes by 47% and 95% respectively vs vehicle control 24h post Con A. JKB-122 significantly inhibited Con A-induced pathological lesions in the liver and the amount of IFN-γ IL-1β, IL-4, IL-5, IL-6, IL-17A and TNF-α starting as early as 3h post Con A. Moreover, JKB-122 given concurrently (× 3 doses) with Con A showed similar effect. Finally, JKB-122 enhanced the therapeutic effects of submaximal dose of prednisolone with improved lesion score. It is concluded that JKB-122 at 20 and 50mg/kg po caused dose-dependent inhibition of elevated liver enzymes in Con A-induced hepatitis in mice, indicating hepatoprotectant activity. The results suggest that JKB-122 as monotherapy or in combination with prednisolone may offer a viable approach to the treatment of AIH.


Sensorineural deafness and labyrinth damage due to lymphocytic choriomeningitis. Report of a case.
Lymphocytic choriomeningitis (LCM) occurred in a hamster handler, produced a "flu"-like illness, and caused unilateral sensorineural deafness and labyrinth damage. Unilateral sensorineural deafness and labyrinth damage caused by LCM virus have not been previously described in the literature.


Revalidation: The professional development discussion.
The professional development discussion (PDD) will be an essential component of revalidation with the Nursing and Midwifery Council. The Unite/CPHVA professional officers who participated in the pilot found the PDD to be the most beneficial part of the revalidation process. This article explores the experience of a PDD from both the revalidatee and the fellow registrant perspective. It goes on to make recommendations for ensuring an effective PDD.